Method for using potassium channel activation for delivering a medicant to an abnormal brain region and/or a malignant tumor

a technology of potassium channel and medicant, applied in the field of medical arts, can solve the problems of limited efficacy of novel therapeutic agents, inability to reach their targets in vivo in adequate quantities, and low permeability to macromolecules and viral particles, so as to reduce the damage to non-malignant tissue, increase the selectivity of drug delivery, and reduce the effect of tumor growth

Inactive Publication Date: 2005-07-14
CEDARS SINAI MEDICAL CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent describes a new way to treat brain tumors or any type of malignant tumor that has increased its ability to take up a specific substance called a potassium channel activator. By giving this substance along with another medicine designed to target the tumor cells specifically, researchers hope they can improve treatment outcomes while reducing harmful side effects for cancer patients.

Problems solved by technology

The patent text discusses the use of potassium channel activators or agonists to treat brain and cerebral tumors by enhancing the delivery of these therapeutic agents through the blood-brain barrier. However, the use of these agents can cause a decrease in blood pressure and may lead to brain edema. The patent aims to address this problem by developing new methods to improve the effectiveness of these agents through the use of potassium channel inhibitors and the inhibition of nitric oxide synthase. The patent also discusses the role of KCa channels in vasodilatation and the use of KCa channel activators and inhibitors for the treatment of malignant tumors. The patent text also describes the use of nitric oxide and potassium channel agonists to increase the effectiveness of therapeuclin and cyclic guanosine monophosphates the KCa channel in the central nervous system. The patent text also discusses the use of nitric oxide and potassium channel activators to treat brain and cerebral tumors. The invention aims to improve the effectiveness of these agents by enhancing their selective transvascular delivery and inhibiting their action on blood pressure and pain recepts. The patent text also describes the use of nitric oxide and KCa channel activators to improve the effectiveness of antic antic antican disorder.

Method used

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  • Method for using potassium channel activation for delivering a medicant to an abnormal brain region and/or a malignant tumor
  • Method for using potassium channel activation for delivering a medicant to an abnormal brain region and/or a malignant tumor
  • Method for using potassium channel activation for delivering a medicant to an abnormal brain region and/or a malignant tumor

Examples

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example 1

Methods

[0080] Malignant Cell Line and Tumor Implantation. A rat glioma cell line, RG2, was used for implantation of experimental brain tumors in female Wistar rats. The techniques for RG2 cell propagation and maintenance in tissue culture have been described (Sugita, M. and Black, K. L., Cyclic GMP-specific phosphodiesterase inhibition and intracarotid bradykinin infusion enhances permeability into brain tumors, Cancer Res. 58(5): 914-20 [1998]; Inamura et al. [1994]; Nakano, S. et al., Increased brain tumor microvessel permeability after intracarotid bradykinin infusion is mediated by nitric oxide, Cancer Res. 56(17): 4027-31 [1996]). Briefly, RG2 cells derived from a rat glioma are kept frozen until use, then are thawed and maintained in a monolayer culture in F12 medium with 10% calf serum.

[0081] The Wistar rats (approximately 140-160 g body weight) were anesthetized with intra-peritoneal ketamine (50 mg / kg), and glial cells (1×105) were implanted into the right hemisphere, but...

example 2

Results

Potassium Channel Activators Selectively Increase Transport Across the Blood-Tumor Barrier.

[0098] When Wistar rats bearing implanted glioma cells were infused with either NS-1619 or minoxidil sulfate, at 7.5 μg kg−1min−1 for 15 minutes, the unidirectional transport constant K for [14C]α-aminoisobutyric acid (AIB) was significantly increased by NS-1619 and minoxidil sulfate with respect to transport across the neovasculature forming the blood-tumor barrier, but not with respect to transport across normal brain microvasculature (data not shown). These results demonstrated that activation of potassium calcium channels selectively increases the permeability of molecules across the capillaries of solid malignant tumors compared to capillaries supplying normal brain tissue.

[0099] Increasing the dose of NS-1619 resulted in an increase in the unidirectional transfer constant Ki for [14C]α-aminoisobutyric acid in RG2 glioma capillaries in a dose-dependent manner (data not shown). ...

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Abstract

Disclosed are methods of selectively delivering a medicant to an abnormal brain region and/or to a malignant tumor in a mammalian subject, including a human. A medicant is administered simultaneously or substantially simultaneously with a potassium channel activator (other than bradykinin or a bradykinin analog), such as an activator of soluble guanylyl cyclase (e.g., nitric oxide or a nitric oxide donor) or an activator of cyclic GMP-dependent protein kinase, whereby the medicant is delivered selectively to the cells of the abnormal brain region and/or to the tumor, compared to normal tissues. Thus, among the disclosures is a method of treating a malignant tumor in a human subject. Also disclosed are pharmaceutical compositions that combine a potassium channel activator together with a medicant and a kit for enhancing the delivery of a medicant to an abnormal brain region and/or to a malignant tumor.

Description

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Claims

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Application Information

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Owner CEDARS SINAI MEDICAL CENT
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